The following articles comprise an overview of work in this area. Each of the publications contains citations to additional references.
EDTA has been encapsulated in liposomes and injected as a treatment for heavy metal poisoning. Tissue uptake of the EDTA in soft tissues such as the liver is said to increase some 20-fold over direct injection of non-encapsulated EDTA. Problems with liposome preparation and pulmonary embolisms are mentioned. Rahman, et al., J. Lab. Clin. Med. 83 (4), 640-7 (1974) and U.S. Pat. No. 3,932,657, issued Jan. 13, 1976, assigned to The U.S. Energy Research and Development Administration.
The oral administration of insulin by encapsulation within lecithin/cholesterol liposomes is reported in FEBS Letters 62, 1, 60-3 (1976) by Patel, et al. See also The Republic of South Africa Application for Patent Ser. No. 73/1850, which discloses and claims the use of various liposome-forming materials to encapsulate insulin for oral delivery.
Liposome materials containing a humectant and their use for moisturizing skin by topical application are disclosed in U.S. Pat. No. 3,957,971, issued May 18, 1976.
The U.S. Energy Research and Development Administration has filed U.S. Patent Application Ser. No. 513,210 (Oct. 19, 1974), now U.S. Pat. No. 3,993,754, which encompasses actinomycin D encapsulated in liposomes for cancer chemotherapy. This application has been laid open to the public as being available for licensing. A research report relative to the patent appears in the Proceedings of The Society for Experimental Biology and Medicine 146, 1173-76 (1974).
Belgian Pat. No. 830,629 (1975) discloses and claims immunologically active compositions characterized by an immunologically effective agent incorporated in a negatively charged liposome. Some of the agents thus encapsulated include virus antigens, bacterial antigens, and the like.
Liposomes comprising certain galactosyl lipids are described in Immunochemistry, Vol. 11, 475-81 (1974) by workers at the Walter Reed Army Institute of Research. Other work on galactosyl lipid membranes has been carried out at the Pasteur Institute (ibid. Vol. 13, 289-94) and elsewhere, as reported in Biochimica et Biophysica Acta 311, 531-44 (1973). These latter publications do not appear to report the preparation of liposomes from the membrane material.
U.S. Pat. No. 3,937,668, issued Feb. 10, 1976, discloses insulin encapsulated in albumin millimicrospheres.
Battelle Memorial Institute-International Division has disclosed a means for encapsulating various water-soluble drugs in liposomes using an ultrasonic vibration technique. German Offen. No. 2,532,317 (1974).
An entirely different class of encapsulating vesicles called "UFASOMES" have been prepared from Unsaturated Fatty Acids and are reported to closely resemble phospholipid liposomes in their structure and properties. Gebicki, et al., Chem. Phys. Lipids 16 (2), 142-60 (1976).
The New England Journal of Medicine, Sept. 23, 1976, pages 704-10 and Sept. 30, 1976, pages 765-70 comprises an extensive report on liposomes, their use in drugs, and contains multiple references to the types of drug agents encapsulated in liposomes.
A review article appearing in the Journal of Lipid Research 9, 310-18 (1968) discloses various general aspects about liposomes and their formation. Another article appearing in Laboratory Investigation 34, No. 3, 276, et. seq. (1976) discusses the entrapment of liposomes in the liver. The in vivo fate and distribution of synthetic lipid vesicles has been studied and reported in the Proceedings of the National Academy of Sciences 71, No. 9, 3487-91 (Sept. 1974). In this study, radioactive technetium was used to monitor the fate of the liposomes. Another study in tumor bearing mice appears in Life Sciences 17, 715-24.
The injection of drugs, including insulin, into rats to study the duration of intramuscular absorption is reported in Chem. Pharm. Bull. 23 (10) 2218-22 (1975).
J. Arehart-Treichel, Science News, Vol. 114, No. 4 (July 22, 1978) at page 60 reports that some workers have tagged liposomes with antibodies to help direct liposomal-packaged enzymes to appropriate target cells for the management of certain disease states.
A particularly relevant article with regard to the present invention is by Mauk and Gamble, Proc. Natl. Acad. Sci. USA, 76, No. 2, pp. 756-769, February, 1979, Biophysics. In that article, the authors report experiments relating to the work of Lunny and Ashwell (Proc. Natl. Acad. Sci, USA, 73, 341-343, 1976) that raised the possibility that surface carbohydrates may serve as determinants for recognition of liposomes by particular tissues. The work of Lunney and Ashwell describes a specific hepatic receptor capable of recognizing and binding galactose-terminated glycoproteins. However, the work of Mauk and Gamble shows that the presence of either fucose or galactose on the surface of the particular vesicles they studied causes "no statistically significant alteration in the tissue distribution of the vesicles."
Gregoriadis, Biochemical Society Transactions, Vol. 3 (1975) p. 613 reports the delivery of bleomycin and radioisotopes (but not insulin or interferon) to the liver using liposomes comprising asialofetuin. (Asialofetuin contains a galactosyl unit.) The work indicates that liver uptake over controls was enhanced, but the statistical significance of the data is unclear.
U.S. Pat. No. 4,016,100, issued Apr. 5, 1977, discloses a pharmaceutical composition which is prepared by dispersing a phospholipid in water, adding a medicament to the aqueous dispersion, freezing said aqueous dispersing to entrap the medicament in lipid spherules, and then thawing the frozen dispersion to give an aqueous suspension of the medicament entrapped in the lipid spherules.
U.S. Pat. No. 4,016,290, issued Apr. 5, 1977, discloses a method for transferring chelating agents across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes are taken up by the cells.
U.S. Pat. No. 4,078,052, issued Mar. 7, 1978, discloses unilamellar vesicles which encapsulate a drug.
The Lancet, June 29, 1974, pp. 1313-1316, discloses the possibility of using liposomes as carriers of drugs in patients with metastatic cancer.
Shipley, Biochimica et Biophysica Acta 311 (1973) 531-544 discloses the phase behavior in water of mono- and digalactosyl diglycerides. The phase behavior of glycolipids and phospholipids are compared and considered in terms of their respective roles in plant and animal cell membranes.